DESCRIPTION: (Applicant's Description) Melanoma is the most malignant of skin cancers. In the USA, the incidence of melanoma is increasing more rapidly than any other cancer. Melanoma is the most frequently occurring cancer in women from the ages of 25-30, and has recently replaced leukemia as responsible for the most lost work hours in the United States. Currently there is no approved therapy that achieves more that a 20% response rate. Therefore, better therapies for malignant melanoma are urgently needed. Introgen Therapeutics is developing a novel anti-tumor gene therapeutic, Ad-mda7, and has demonstrated it's anti-tumor potential against breast and lung cancer cell lines. Here, we propose to perform proof-of-principle experiments to evaluate the efficacy of Ad-mda7 in melanoma. Growth inhibition studies will be performed using human melanoma cell lines in vitro and, if successful, will progress to evaluate Ad-mda7 in vivo using human melanoma xenografts. If these first aims are successful, we will test Ad-mda7 alone and in combination with conventional chemotherapeutic agents using metastatic tumor models. At the end of this Phase I STTR, we plan to have gathered the necessary efficacy data to proceed to safety studies and IND filing in a Phase II STTR, based on clinical trial testing of Ad-mda7. PROPOSED COMMERCIAL APPLICATION: Ad-mda7 is a gene therapy drug to be tested as a novel therapeutic for the treatment of malignant melanoma. Malignant melanoma is a dire skin cancer with few available treatment options. The incidence of melanoma and malignant melanoma is increasing. Approximately 41,000 people are predicted to diagnosed with melanoma this year, with more than 7,000 deaths resulting from this disease. The studies outlined here will guide the preclinical development of Ad-mda7 for melanoma. Subsequent Phase II studies will evaluate the therapeutic potential of Ad-mda7 in clinical trials with the goal of submission of a BLA to the FDA and subsequent marketing.